Impact of Effective Refractory Period Personalisation on Arrhythmia Vulnerability in Patient-Specific Atrial Computer Models.

BACKGROUND AND AIMS: The effective refractory period (ERP) is one of the main electrophysiological properties governing arrhythmia, yet ERP personalisation is rarely performed when creating patient-specific computer models of the atria to inform clinical decision-making. This study evaluates the impact of integrating clinical ERP measurements into personalised in silico models on arrhythmia vulnerability. METHODS: Clinical ERP measurements were obtained in seven patients from multiple locations in the atria. Atrial geometries from the electroanatomical mapping system were used to generate personalised anatomical atrial models. The Courtemanche cellular model was adjusted to reproduce patientspecific ERP. Four modelling approaches were compared: homogeneous (A), heterogeneous (B), regional (C), and continuous (D) ERP distributions. Non-personalised approaches (A, B) were based on literature data, while personalised approaches (C, D) were based on patient measurements. Modelling effects were assessed on arrhythmia vulnerability and tachycardia cycle length, with sensitivity analysis on ERP measurement uncertainty. RESULTS: Mean vulnerability was 3.4±4.0%, 7.7±3.4%, 9.0±5.1%, 7.0±3.6% for scenarios A to D, respectively. Mean tachycardia cycle length was 167.1±12.6 ms, 158.4±27.5 ms, 265.2±39.9 ms, and 285.9±77.3 ms for scenarios A to D, respectively. Incorporating perturbations to the measured ERP in the range of 2, 5, 10, 20, and 50ms changed the vulnerability of the model to 5.8±2.7%, 6.1±3.5%, 6.9±3.7%, 5.2±3.5%, 9.7±10.0% respectively. CONCLUSION: Increased ERP dispersion had a greater effect on reentry dynamics than on vulnerability. Inducibility was higher in personalised scenarios compared to scenarios with uniformly reduced ERP; however, this effect was reversed when incorporating fibrosis informed by low voltage areas.ERP measurement uncertainty up to 20 ms slightly influenced vulnerability. Electrophysiological personalisation of atrial in silico models appears essential and requires confirmation in larger cohorts.

Lower diastolic tension may be indicative of higher proarrhythmic propensity in failing human cardiomyocytes.

Chronic heart failure is one of the most common reasons for hospitalization. Current risk stratification is based on ejection fraction, whereas many arrhythmic events occur in patients with relatively preserved ejection fraction. We aim to investigate the mechanistic link between proarrhythmic abnormalities, reduced contractility and diastolic dysfunction in heart failure, using electromechanical modelling and simulations of human failing cardiomyocytes. We constructed, calibrated and validated populations of human electromechanical models of failing cardiomyocytes, that were able to reproduce the prolonged action potential, reduced contractility and diastolic dysfunction as observed in human data, as well as increased propensity to proarrhythmic incidents such as early afterdepolarization and beat-to-beat alternans. Our simulation data reveal that proarrhythmic incidents tend to occur in failing myocytes with lower diastolic tension, rather than with lower contractility, due to the relative preserved SERCA and sodium calcium exchanger current. These results support the inclusion of end-diastolic volume to be potentially beneficial in the risk stratifications of heart failure patients.

Characterization of natural product inhibitors of quorum sensing reveals competitive inhibition of Pseudomonas aeruginosa RhlR by ortho-vanillin.

Quorum sensing (QS) is a cell-cell signaling system that enables bacteria to coordinate population density-dependent changes in behavior. This chemical communication pathway is mediated by diffusible N-acyl L-homoserine lactone signals and cytoplasmic signal-responsive LuxR-type receptors in Gram-negative bacteria. As many common pathogenic bacteria use QS to regulate virulence, there is significant interest in disrupting QS as a potential therapeutic strategy. Prior studies have implicated the natural products salicylic acid, cinnamaldehyde, and other related benzaldehyde derivatives as inhibitors of QS in the opportunistic pathogen Pseudomonas aeruginosa, yet we lack an understanding of the mechanisms by which these compounds function. Herein, we evaluate the activity of a set of benzaldehyde derivatives using heterologous reporters of the P. aeruginosa LasR and RhlR QS signal receptors. We find that most tested benzaldehyde derivatives can antagonize LasR or RhlR reporter activation at micromolar concentrations, although certain molecules also cause mild growth defects and nonspecific reporter antagonism. Notably, several compounds showed promising RhlR or LasR-specific inhibitory activities over a range of concentrations below that causing toxicity. ortho-Vanillin, a previously untested compound, was the most promising within this set. Competition experiments against the native ligands for LasR and RhlR revealed that ortho-vanillin can interact competitively with RhlR but not with LasR. Overall, these studies expand our understanding of benzaldehyde activities in the LasR and RhlR receptors and reveal potentially promising effects of ortho-vanillin as a small molecule QS modulator against RhlR. IMPORTANCE: Quorum sensing (QS) regulates many aspects of bacterial pathogenesis and has attracted much interest as a target for anti-virulence therapies over the past 30 years, for example, antagonists of the LasR and RhlR QS receptors in Pseudomonas aeruginosa. Potent and selective QS inhibitors remain relatively scarce. However, natural products have provided a bounty of chemical scaffolds with anti-QS activities, but their molecular mechanisms are poorly characterized. The current study serves to fill this void by examining the activity of an important and wide-spread class of natural product QS modulators, benzaldehydes, and related derivatives, in LasR and RhlR. We demonstrate that ortho-vanillin can act as a competitive inhibitor of RhlR, a receptor that has emerged and may supplant LasR in certain settings as a target for P. aeruginosa QS control. The results and insights provided herein will advance the design of chemical tools to study QS with improved activities and selectivities.

In Silico TRials guide optimal stratification of ATrIal FIbrillation patients to Catheter Ablation and pharmacological medicaTION: the i-STRATIFICATION study.

AIMS: Patients with persistent atrial fibrillation (AF) experience 50% recurrence despite pulmonary vein isolation (PVI), and no consensus is established for secondary treatments. The aim of our i-STRATIFICATION study is to provide evidence for stratifying patients with AF recurrence after PVI to optimal pharmacological and ablation therapies, through in silico trials. METHODS AND RESULTS: A cohort of 800 virtual patients, with variability in atrial anatomy, electrophysiology, and tissue structure (low-voltage areas, LVAs), was developed and validated against clinical data from ionic currents to electrocardiogram. Virtual patients presenting AF post-PVI underwent 12 secondary treatments. Sustained AF developed in 522 virtual patients after PVI. Second ablation procedures involving left atrial ablation alone showed 55% efficacy, only succeeding in the small right atria (<60 mL). When additional cavo-tricuspid isthmus ablation was considered, Marshall-PLAN sufficed (66% efficacy) for the small left atria (<90 mL). For the bigger left atria, a more aggressive ablation approach was required, such as anterior mitral line (75% efficacy) or posterior wall isolation plus mitral isthmus ablation (77% efficacy). Virtual patients with LVAs greatly benefited from LVA ablation in the left and right atria (100% efficacy). Conversely, in the absence of LVAs, synergistic ablation and pharmacotherapy could terminate AF. In the absence of ablation, the patient's ionic current substrate modulated the response to antiarrhythmic drugs, being the inward currents critical for optimal stratification to amiodarone or vernakalant. CONCLUSION: In silico trials identify optimal strategies for AF treatment based on virtual patient characteristics, evidencing the power of human modelling and simulation as a clinical assisting tool.

Influence of Hospital Type on Outcomes of Patients With Acute Spontaneous Intracerebral Hemorrhage: A Population-Based Study.

BACKGROUND AND OBJECTIVES: Whether the outcome of patients with spontaneous intracerebral hemorrhage (ICH) differs depending on the type of hospital where they are admitted is uncertain. The objective of this study was to determine influence of hospital type at admission (telestroke center [TSC], primary stroke center [PSC], or comprehensive stroke center [CSC]) on outcome for patients with ICH. We hypothesized that outcomes may be better for patients admitted to a CSC. METHODS: This is a multicenter prospective observational and population-based study of a cohort of consecutively recruited patients with ICH (March 2020-March 2022). We included all patients with spontaneous ICH in Catalonia (Spain) who had a pre-ICH modified Rankin scale (mRS) score of 0-3 and who were admitted to the hospital within 24 hours of onset. We compared patients admitted to a TSC/PSC (n = 641) or a CSC (n = 1,320) and also analyzed the subgroup of patients transferred (n = 331) or not transferred (n = 310) from a TSC/PSC to a CSC. The main outcome was the 3-month mRS score obtained by blinded investigators. Outcomes were compared using adjusted ordinal logistic regression to estimate the common odds ratio (OR) and 95% CI for a shift in mRS scores. A propensity score matching (PSM) analysis was performed for the subgroup of transferred patients. RESULTS: Relevant data were obtained from 1961 of a total of 2,230 patients, with the mean (SD) age of 70 (14.1) years, and 713 (38%) patients were women. After adjusting for confounders (age, NIH Stroke Scale score, intraventricular hemorrhage, hematoma volume, and pre-ICH mRS score), type of hospital of initial admission (CSC vs TSC/PSC) was not associated with outcome (adjusted common OR 1.13, 95% CI 0.93-1.38). A PSM analysis indicated that transfer to a CSC was not associated with more favorable outcomes (OR 0.77, 95% CI 0.55-1.10; p = 0.16). DISCUSSION: In this population-based study, we found that, after adjusting for confounders, hospital types were not associated with functional outcomes. In addition, for patients who were transferred from a TSC/PSC to a CSC, PSM indicated that outcomes were similar to nontransferred patients. Our findings suggest that patient characteristics are more important than hospital characteristics in determining outcome after ICH. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03956485.

Characterization of natural product inhibitors of quorum sensing in Pseudomonas aeruginosa reveals competitive inhibition of RhlR by ortho-vanillin.

Quorum sensing (QS) is a cell-cell signaling system that enables bacteria to coordinate population density-dependent changes in behavior. This chemical communication pathway is mediated by diffusible N-acyl L-homoserine lactone signals and cytoplasmic signal-responsive LuxR-type receptors in Gram-negative bacteria. As many common pathogenic bacteria use QS to regulate virulence, there is significant interest in disrupting QS as a potential therapeutic strategy. Prior studies have implicated the natural products salicylic acid, cinnamaldehyde and other related benzaldehyde derivatives as inhibitors of QS in the opportunistic pathogen Pseudomonas aeruginosa, yet we lack an understanding of the mechanisms by which these compounds function. Herein, we evaluate the activity of a set of benzaldehyde derivatives using heterologous reporters of the P. aeruginosa LasR and RhlR QS signal receptors. We find that most tested benzaldehyde derivatives can antagonize LasR or RhlR reporter activation at micromolar concentrations, although certain molecules also caused mild growth defects and nonspecific reporter antagonism. Notably, several compounds showed promising RhlR or LasR specific inhibitory activities over a range of concentrations below that causing toxicity. Ortho-Vanillin, a previously untested compound, was the most promising within this set. Competition experiments against the native ligands for LasR and RhlR revealed that ortho-vanillin can interact competitively with RhlR but not with LasR. Overall, these studies expand our understanding of benzaldehyde activities in the LasR and RhlR receptors and reveal potentially promising effects of ortho-vanillin as a small molecule QS modulator against RhlR.

Digital twinning of the human ventricular activation sequence to Clinical 12-lead ECGs and magnetic resonance imaging using realistic Purkinje networks for in silico clinical trials.

Cardiac in silico clinical trials can virtually assess the safety and efficacy of therapies using human-based modelling and simulation. These technologies can provide mechanistic explanations for clinically observed pathological behaviour. Designing virtual cohorts for in silico trials requires exploiting clinical data to capture the physiological variability in the human population. The clinical characterisation of ventricular activation and the Purkinje network is challenging, especially non-invasively. Our study aims to present a novel digital twinning pipeline that can efficiently generate and integrate Purkinje networks into human multiscale biventricular models based on subject-specific clinical 12-lead electrocardiogram and magnetic resonance recordings. Essential novel features of the pipeline are the human-based Purkinje network generation method, personalisation considering ECG R wave progression as well as QRS morphology, and translation from reduced-order Eikonal models to equivalent biophysically-detailed monodomain ones. We demonstrate ECG simulations in line with clinical data with clinical image-based multiscale models with Purkinje in four control subjects and two hypertrophic cardiomyopathy patients (simulated and clinical QRS complexes with Pearson's correlation coefficients > 0.7). Our methods also considered possible differences in the density of Purkinje myocardial junctions in the Eikonal-based inference as regional conduction velocities. These differences translated into regional coupling effects between Purkinje and myocardial models in the monodomain formulation. In summary, we demonstrate a digital twin pipeline enabling simulations yielding clinically consistent ECGs with clinical CMR image-based biventricular multiscale models, including personalised Purkinje in healthy and cardiac disease conditions.

Toward Enabling Cardiac Digital Twins of Myocardial Infarction Using Deep Computational Models for Inverse Inference.

Cardiac digital twins (CDTs) have the potential to offer individualized evaluation of cardiac function in a non-invasive manner, making them a promising approach for personalized diagnosis and treatment planning of myocardial infarction (MI). The inference of accurate myocardial tissue properties is crucial in creating a reliable CDT of MI. In this work, we investigate the feasibility of inferring myocardial tissue properties from the electrocardiogram (ECG) within a CDT platform. The platform integrates multi-modal data, such as cardiac MRI and ECG, to enhance the accuracy and reliability of the inferred tissue properties. We perform a sensitivity analysis based on computer simulations, systematically exploring the effects of infarct location, size, degree of transmurality, and electrical activity alteration on the simulated QRS complex of ECG, to establish the limits of the approach. We subsequently present a novel deep computational model, comprising a dual-branch variational autoencoder and an inference model, to infer infarct location and distribution from the simulated QRS. The proposed model achieves mean Dice scores of 0.457 ±0.317 and 0.302 ±0.273 for the inference of left ventricle scars and border zone, respectively. The sensitivity analysis enhances our understanding of the complex relationship between infarct characteristics and electrophysiological features. The in silico experimental results show that the model can effectively capture the relationship for the inverse inference, with promising potential for clinical application in the future. The code is available at https://github.com/lileitech/MI_inverse_inference.

Palatability and Stability Studies to Optimize a Carvedilol Oral Liquid Formulation for Pediatric Use.

Carvedilol (CARV) is a blocker of α- and ß- adrenergic receptors, used as an "off-label" treatment for cardiovascular diseases in pediatrics. Currently, there is no marketed pediatric-appropriate CARV liquid formulation, so its development is necessary. Palatability (appreciation of smell, taste, and aftertaste) is a key aspect to be considered during the development of pediatric formulations since only formulations with good palatability also have adequate acceptability in this population. Consequently, the aim of this research was to assess the palatability and acceptability of different CARV formulations using an in vivo taste assessment (ID Number PR103/22) in order to select the highest palatability-rated CARV formulation. The preparation of CARV formulations was based on a reference 1 mg/mL CARV solution, which contains malic acid as a solubilizing agent. Subsequently, sucralose and flavoring agents were added and mixed until complete dissolution to the corresponding formulations. Adult volunteers participated in this study and evaluated the taste and odor of various CARV formulations through a questionnaire and a sensory test. The mean palatability score, measured on a 10-point scale, increased from 1.60 for the unflavored control to 7.65 for the highest-rated flavored formulation. Moreover, the bitterness of the optimized CARV formulation was reduced from 66.67% to 17.86%, and the taste pleasantness was increased from 25/100 to 73/100. This optimized CARV formulation contains a sweetening agent, sucralose, in addition to two flavoring agents at appropriate concentrations for pediatrics. Furthermore, the physicochemical and microbiological stability of the optimized CARV formulation were evaluated for 6 months at 25, 30, and 40 °C, in addition to in-use stability for 15 days at 25 °C, whose results were confirmed. Thus, we successfully developed a palatable CARV liquid solution that contains excipients appropriate for pediatrics and is stable under the studied conditions.

Patrones clínicos e histopatológicos de dermatosis en pacientes con infección por COVID-19 en la Unidad Médica de Alta Especialidad del Bajío, IMSS-T1, de León, Guanajuato / Clinical and histopathological patterns of dermatosis in COVID-19 positive patients treated in the Unidad Médica de Alta Especialidad del Bajío, IMSS-T1, de León, Guanajuato

INTRODUCCIÓN: La enfermedad COVID-19, además de presentar síntomas respiratorios, puede afectar otros órganos como la piel. Al momento, se han descrito cinco variantes clínicas de manifestaciones cutáneas por COVID-19. Pocos reportes abordan el tema de la gravedad de las dermatosis cutáneas de COVID-19 y el pronóstico. OBJETIVO: Describir patrones clínicos e histológicos de dermatosis en pacientes con COVID-19. Pacientes y MÉTODOS: Es una cohorte para pacientes del IMSS-T1 en León, Guanajuato, México, entre septiembre 2020 y enero 2021. Identificamos pacientes con dermatosis asociada a COVID-19 desde su ingreso hospitalario y aquellos que la desarrollaron durante su estancia. Se les invitó a participar para evaluación clínica y toma de biopsia que fueron descritas por un patólogo experto. RESULTADOS: La frecuencia de las dermatosis por COVID-19 fue de 15,7%. Los que desarrollaron las lesiones durante su estancia hospitalaria presentaron mayor morbi-mortalidad (p = 0,001). Las lesiones vaso-oclusivas fueron las más diagnosticadas y asociadas con mayor mortalidad (p = 0,003). Histológicamente el hallazgo más común fue trombosis superficial y profunda (58%). CONCLUSIONES: Los pacientes que desarrollaron las lesiones durante su hospitalización y aquellos con lesiones vaso-oclusivas tuvieron la mayor morbi-mortalidad. Las lesiones vaso-oclusivas pueden ser un factor de mal pronóstico en pacientes con COVID-19.

BACKGROUND: COVID-19 disease, besides presenting respiratory manifestations, can affect other organs such as kidneys, gastrointestinal system, heart, and skin. So far, five clinical variants of dermatoses have been described. Few reports discuss the severity associated with the cutaneous manifestations of COVID-19 and the prognosis. AIM: To describe the clinical and histopathological patterns of dermatoses in patients with COVID-19 infection. PATIENTS AND METHODS: Prospective cohort study conducted in patients admitted to "IMSS T1" in Leon, Guanajuato, Mexico from September 2020 to January 2021. We identified those with COVID-19 dermatosis from the moment they were admitted; and those who developed them during hospitalization. Patients were invited to participate for a clinical evaluation and biopsy. The biopsies were described by an expert pathologist. RESULTS: The frequency of dermatological lesions was 15.7%. Those who developed dermatosis during their hospital stay presented higher mortality (p = 0.001) and severity of COVID-19 (p = 0.001) Vasoocclusive lesions were the most frequent in the hospital setting, and were associated to higher mortality (p = 0.003). The most frequent histopathological feature was superficial and deep thrombosis (58%). CONCLUSIONS: Patients who developed dermatologic lesions during hospitalization and those with vaso-occlusive dermatoses had higher morbi-mortality. Vaso-occlusive lesions could be considered as a poor prognostic factor.

Tuberculosis vertebral / Spinal tuberculosis

Introducción: la tuberculosis es una enfermedad infecciosa. Es una importante causa de incapacidad y muerte en muchas zonas del mundo. Además de la localización pulmonar, que es la más frecuente, puede ocurrir una diseminación del bacilo hacia otros órganos, dando lugar a la llamada tuberculosis extrapulmonar, que puede afectar cualquier órgano o tejido, incluyendo la columna vertebral. Caso clínico: se presenta un caso con tuberculosis vertebral en un paciente de una institución cerrada de la ciudad de Pinar del Río; este debutó inicialmente con síntomas respiratorios y toma del estado general. Se le realizó una tomografía axial computarizada de mediastino que mostró lesiones óseas a nivel vertebral. El tratamiento actual resultó favorable. Conclusiones: la forma clínica extrapulmonar es de presentación menos frecuente, sin embargo, su diagnóstico es de mucha importancia en este grupo poblacional muy vulnerable.

Introduction: tuberculosis is an infectious disease. It is a major cause of disability and death in many parts of the world. Pulmonary location is the most common, where a dissemination of the bacillus may occur and infect other organs and tissues, leading to extrapulmonary tuberculosis, including the spine. Clinical case: the case of a patient admitted in a closed-treatment unit in Pinar del Río city presented vertebral extrapulmonary tuberculosis, who initially presented respiratory symptoms and poor general status. A computed tomography [CT] of the mediastinum showed osseous lesions at vertebral level. Current treatment provided a favorable improvement. Conclusions: extrapulmonary clinical presentation is less common; however, its diagnosis is very important for this very vulnerable population group.

Evaluación del Programa de Tuberculosis en instituciones cerradas / Evaluation of the Tuberculosis Program in closed institutions

Introducción: las evaluaciones son vitales para el éxito de cualquier programa al medir y analizar el cumplimiento de los objetivos trazados. La más utilizada se basa en la evaluación de los tres componentes: estructura, proceso y resultados. Objetivo: evaluar el programa nacional de control de la tuberculosis en instituciones cerradas de Pinar del Río. Material y método: se realizó una investigación evaluativa, con un diseño de estudio descriptivo retrospectivo. Se definieron criterios y variables, escala de clasificación, descripción operacional con indicadores y estándares en los tres componentes del programa. La información se obtuvo de registros estadísticos, historias y cuadro epidemiológico. Se realizó la evaluación de los indicadores, comparando el resultado obtenido con los estándares establecidos en el programa nacional de control de la tuberculosis del Ministerio de Salud Pública de Cuba y otros fijados por las instituciones cerradas de salud, otorgándoles las categorías de bien, regular o mal. Resultados: se identificó la adecuada cobertura, capacitación de recursos humanos, materiales y el control de calidad en el componente de estructura, interrupciones en el tratamiento de quimioprofilaxis de los contactos, diagnósticos tardíos y realizados en la atención secundaria de salud en el componente de proceso, media de edad de 36 años, incremento en la incidencia y predominio en la institución cerrada provincial como los principales del componente de resultados. Conclusiones: el programa se evaluó de regular. La investigación permitió identificar brechas existentes en las acciones de prevención y control realizadas, aportando evidencias objetivas y científicas del funcionamiento del mismo, útiles en la toma de decisiones.

Introduction: assessments are vital to the success of any program to measure and analyze the fulfillment of the objectives. The most commonly used is based on the evaluation of three components: structure, process and results. Objective: to evaluate the national program for tuberculosis control in closed institutions of Pinar del Río. Material and method: an evaluative research was conducted with a retrospective study design. Criteria and variables, rating scale, operational description indicators and standards in the three components of the program were defined. The information was obtained from statistical records, histories and epidemiological picture. The evaluation of indicators was conducted by comparing the results obtained with the standards established in the national program for tuberculosis control of the Ministry of Public Health of Cuba and other closed institutions set by health, giving the categories of good, fair or wrong. Results: adequate coverage, training of human resources, materials and quality control in the component structure, treatment interruptions chemoprophylaxis of contacts made in late diagnosis and secondary health care in the process component identified , average age 36, increased incidence and prevalence in the provincial closed institution as the main component results. Conclusions: the program is evaluated regularly. The research identified gaps in the prevention and control actions carried out by providing objective and scientific operation thereof, useful in decision making evidence.

Efectividad y seguridad de la cefotaxima para el tratamiento de niños con meningitis bacteriana aguda / Effectiveness and safety of cefotaxime for the treatment of children with acute bacterial meningitis

Introducción: la cefotaxima es una opción para el tratamiento de la meningitis bacteriana aguda asociada a la comunidad. Esta evaluación tecnológica se desarrolló en el marco de la actualización integral del Plan Obligatorio de Salud para el año 2015. Objetivo: evaluar la efectividad y seguridad de la cefotaxima como terapia empírica de primera línea en monoterapia y en combinación con ampicilina o vancomicina, comparada con ceftriaxona, ampicilina más cefepime, ampicilina más cloranfenicol, ampicilina más gentamicina y ceftriaxona más vancomicina, para meningitis bacteriana aguda asociada a la comunidad en niños. Metodología: la evaluación fue realizada de acuerdo con un protocolo definido a priori por el grupo desarrollador. Se realizó una búsqueda sistemática en MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects y LILACS, sin restricciones de idioma y limitada a revisiones sistemáticas publicadas en los últimos cinco años. Las búsquedas en bases de datos fueron hechas en noviembre de 2014 y se complementaron mediante búsqueda manual en bola de nieve y una consulta con expertos temáticos. La tamización de referencias se realizó por dos revisores de forma independiente y los desacuerdos fueron resueltos por consenso. La selección de estudios fue realizada mediante la revisión en texto completo de las referencias preseleccionadas, verificando los criterios de elegibilidad. Se incluyeron revisiones sistemáticas de ensayos clínicos, su calidad fue valorada con la herramienta AMSTAR. Las características de las revisiones fueron extraídas a partir de las publicaciones originales. Se realizó una síntesis narrativa de las estimaciones del efecto para las comparaciones y desenlaces de interés a partir de los estudios de mejor calidad con AMSTAR. Los meta-análisis se realizaron con el método de Mantel-Haenszel y un modelo de efectos fijos, en el programa RevMan 5.2. Resultados: se seleccionó una revisión sistemática que incluyó 19 ensayos clínicos (1496 pacientes), cuatro de estos ensayos (266 pacientes) fueron relevantes para la pregunta abordada por la presente evaluación. La cefotaxima como monoterapia comparada con ceftriaxona presentó una mayor positividad del cultivo del líquido cefalorraquídeo, para esta misma comparación, la evidencia sobre la mortalidad fue escasa. La cefotaxima en monoterapia comparada con ampicilina-cloranfenicol no presentó una diferencia estadísticamente significativa sobre la mortalidad y se asoció con una reducción estadísticamente significativa de la positividad del cultivo de líquido cefalorraquídeo. La cefotaxima en monoterapia no presentó diferencias estadísticamente significativas frente a la combinación de ampicilina más cloranfenicol o gentamicina para los desenlaces mortalidad, sordera y positividad del cultivo de líquido cefalorraquídeo. La cefotaxima en monoterapia comparada con ceftriaxona se asoció con una reducción estadísticamente significativa en la frecuencia de diarrea, para esta misma comparación, no se presentaron diferencias estadísticamente significativas respecto a otros eventos adversos. No se presentaron diferencias estadísticamente significativas en cuanto a la incidencia de eventos adversos (diarrea, neutropenia y rash en piel) de cefotaxima en monoterapia comparada con ampicilina más cloranfenicol o gentamicina. Conclusiones: el desempeño global de la cefotaxima como monoterapia empírica de primera línea para niños con meningitis bacteriana aguda asociada a la comunidad, muestra que en la mayoría de los desenlaces de efectividad y seguridad los efectos con la cefotaxima son similares frente a sus comparadores. Estas conclusiones se basan en los hallazgos de una revisión sistemática de alta calidad.(AU)

Efectividad y seguridad de Risperidona comparada con Haloperidol, Olanzapina, Clozapina, Quetiapina, Aripiprazol, Clonidina, Placebo en personas con diagnóstico de trastorno del espectro autista - TEA / Effectiveness and Safety of Risperidone compared to Haloperidol, Olanzapine, Clozapine, Quetiapine, Aripiprazole, Clonidine, Placebo in People with Autism Spectrum Disorder - ASD

Introducción: Los trastornos del espectro autista (TEA) son un grupo de discapacidades del desarrollo, de características crónicas y que afectan de manera distinta a cada paciente. Los TEA se definen como una disfunción neurológica crónica con fuerte base genética que desde edades tempranas se manifiesta en una serie de síntomas basados en la tríada de Wing que incluye: la comunicación, flexibilidad e imaginación e interacción social. No existe tratamiento curativo para el TEA, las terapias están dirigidas al control de los síntomas. Debido a la heterogeneidad de los síntomas, las terapias deben adaptarse al caso individual del paciente. Las intervenciones para los pacientes con diagnóstico de TEA pueden incluir educación, terapia conductual, o manejo farmacológico. Objetivo: realizar una revisión, apreciación crítica y síntesis de la evidencia disponible sobre la efectividad y seguridad de la risperidona para el tratamiento de personas con diagnóstico de trastorno del espectro autista. Metodología: la evaluación fue realizada de acuerdo con un protocolo definido a priori por el grupo desarrollador. Se realizó una búsqueda sistemática en MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, LILACS y Google, sin restricciones de idioma, fecha de publicación y tipo de estudio. Las búsquedas electrónicas fueron hechas en octubre de 2014 y se complementaron mediante búsqueda manual en bola de nieve y una consulta con expertos temáticos. La tamización de referencias se realizó por dos revisores de forma independiente y los desacuerdos fueron resueltos por consenso. La selección de estudios fue realizada mediante la revisión en texto completo de las referencias preseleccionadas, verificando los criterios de elegibilidad predefinidos. Las características y hallazgos de los estudios fueron extraídos a partir de las publicaciones originales. Resultados: Se identificó evidencia proveniente de 4 revisiones sistemáticas de moderada y alta calidad, que compraban risperidona con placebo, se encontró que risperidona fue superior a placebo en los desenlaces de impresión global de salud, irritabilidad, hiperactividad, estereotipias. Conclusiones: La risperidona comparada con placebo sugiere efectividad en relación a mejoría de síntomas como irritabilidad, hiperactividad y estereotipias, así como, de la impresión clínica global. No se puede establecer con la evidencia actual el perfil de seguridad de la risperidona, solo se evidenció que los pacientes que reciben risperidona tienen mayor riesgo de aumento de peso y de presentar síndrome de extrapiramidalismo.

Contaminación bacteriana en el agua de unidades dentales de una institución de salud pública / Bacterial contamination in dental unit water from a public health institution

Se evaluó la calidad bacteriológica del agua de 8 clínicas de una institución de salud pública (ISSSTE) de 2 zonas de la ciudad de México, determinándose coliformes fecales y coliformes totales, por medio de la técnica de filtro de membrana, realizándose en 2 diferentes periodos y 3 puntos de muestreo (jeringa triple, llena vasos y suministro) en 9 unidades dentales. De las 8 clínicas analizadas 7 presentaron contaminación bacteriana. Perteneciendo 4 a la zona norte y 3 a la zona sur. El problema de la contaminación en la zona norte se debe principalmente a la mala calidad del agua de suministro la cual en esta zona provenía en su mayoría de las botellas del sistema abastecedor de agua. La otra causa de contaminación se debió a la deficiente o nula desinfección de la jeringa triple. En la zona sur 3 de las 4 clínicas en general presentaron baja contaminación bacteriana solo en el primer periodo, lo cual se puede atribuir a la mejor calidad del agua proveniente de los suministros. Se concluye que los factores determinantes de la presencia de contaminación bacteriana en el agua utilizada en las unidades dentales de ambas zonas fueron: la calidad del agua de suministro y la inadecuada desinfección de la jeringa triple. Mantener una buena calidad de agua en las unidades dentales es muy importante, pues el líquido entra directamente en contacto con la mucosa de cavidad oral, estructuras dentarias, sangre y saliva del paciente, evitando procesos infecciosos que podrían poner en riesgo su salud integral

It was assessed the bacteriological quality of water in 8 clinics of a public health institution (ISSSTE) in 2 areas of Mexico City, determined fecal coliform and total coliform, by means of the technique of membrane filter. There were made 2 different periods and 3 sampling points (syringe triple, flood glasses and supply) in 9 dental units. Of the 8 clinics analyzed 7 presented bacterial pollution. 4 Belonged to the north and 3 to the south zone. The problem of pollution in the north zone is mainly due to the poor water quality of supply which in this area came mostly from the bottles of the flush system. The other source of pollution was due to the poor or non-existent disinfection of the triple syringe. In the south zone in general 3 of 4 clinics presented low bacterial pollution only in the first period, which can be attributed to the better quality of water from the supplies. It concludes that the determining factors in the presence of bacterial pollution in water used in dental units of both areas were: the quality of water supply and inadequate disinfection of the triple syringe. Maintain a good water quality in dental units is very important, because liquid makes direct contact with the mucous membrane of oral cavity, dental structures, blood and saliva of the patient, avoiding infectious processes that could put in risk their integral health

Uso de antibióticos parenterales en el servicio de medicina interna de un hospital de tercer nivel de la ciudad de Bogotá / Parenteral antibiotics utilization in the internal medicine service of a third level hospital from Bogota city

Mediante un estudio observacional y de corte transversal, relacionado con el esquema terapéutico, se describió el consumo y las prácticas de prescripción de antibióticos parenterales en el servicio de medicina interna del Hospital Universitario La Samaritana de Bogotá. Se administraron 32,6 ddd/100 pacientes/día, siendo los grupos terapéuticos más prescritos: cefalosporinas, penicilinas y quinolonas. Los errores en el esquema terapéutico se presentaron en el régimen de dosificación, en la elección del medicamento y en la duración del tratamiento. Del presente estudio se extraen los primeros indicadores de consumo y prescripción para el servicio, estableciendo un punto de referencia para próximas evaluaciones.

A cross-sectional and observational study related with therapeutic plan, was described the utilization and prescription practices of parenteral antibiotics, in the internal medicine service of the Hospital Universitario La Samaritana E.S.E from Bogota city. Were administered 32.6 ddd/100 patients-day. The most prescribed therapeutic groups were: cephalosporins, penicillins and quinolones. The errors in the therapeutic plan were in: the dosification regimen, the drug selection and the therapy duration. From this study were extracted the first consumption and prescription indicators to the service, for establishing a reference point to next evaluations.

Hidrometrocolpos: presentación de un caso / Hydrometrocolpos: presentation of a Case

El hidrometrocolpos es una obstrucción a nivel del tracto genital femenino, que aparece en la etapa neonatal como una masa en hemiabdomen inferior, por encima de la sínfisis del pubis. Presentamos recién nacida pretérmino, con edad gestacional de 33,4 semanas por método de Capurro, producto de parto eutócico, apgar 2/5, peso 1954 gr, que presenta masa abdominal constatada durante la reanimación cardiopulmonar realizada inmediatamente después del nacimiento. Al examen físico posterior se observa la presencia de gran aumento de volumen en región perineal que afecta los genitales externos, borramiento del pliegue interglúteo, e himen imperforado. Durante el estudio se constata riñón poliquístico del lado derecho e hidronefrosis severa del lado izquierdo, así como gran masa intrabdominal de contenido líquido. Se plantea el diagnóstico de hidrometrocolpos y se procede a la realización de intervención quirúrgica que consistió en perforación del himen, obteniéndose la salida de aproximadamente 200ml de líquido procedente de la vagina. Después de lo cual se produce la regresión de las estructuras anatómicas paulatinamente.

The hydrometrocolpos is an obstruction at the level of female genital tract that appears during the neonatal stage as a mass in the lower hemi abdomen, over the synphisis of the pubis. It is presented a 33, 4-weeks-gestational-newborn girl, by means of Bud method, due to a euthocic birth, apgar 5/2, and weight 1954gr, who has an abdominal mass noted during the Cardiopulmonar reanimation made immediately after her birth. In the later physical exam it is observed the presence of a great increasement of volume in the perineal area that affects the external genitals, erasing of the intergluteal fold, imperforated hymen. During this study it is also noted polycystic kidney disease in the right side and a sever hydronephrohydrosis in the left side, as well as a great intra-abdominal mass with a liquid content. The diagnosis of hydrometrocolpus is posed and then a surgery is made to pierce the hymen, obtaining the outlet of 200ml of liquid approximately, coming from the vagina. After this, the regression of the anatomical structures is gradually produced.

Evaluación del efecto terapéutico del quelbén en pacientes con queloides / Evaluation of the therapeutical effect of quelben in patients with keloids

Se realizó un estudio con 80 pacientes en edades comprendidas entre 15 y 25 años, de cualquier raza y sexo que presentan queloides en cualquier parte del cuerpo, dividiéndose en 2 grupos, según tabla aleatoria confeccionada para este fin. Se le aplicó a un grupo un producto denominado quelbén, elaborado a base de lodo termal, y al otro grupo una crema esteroidea al 2 por ciento en un período de 6 meses de tratamiento. La respuesta clínica al tratamiento se midió a través de 3 parámetros: el tamaño de la lesión y el grosor, la consistencia de la lesión, así como los síntomas subjetivos (prurito, dolor, hiperestesias y tirantez) acompañantes de la lesión. La respuesta al tratamiento con el quelbén fue favorable ya sea en pacientes limpios (11) o respondedores (21), lo que representa un 91,43 por ciento en lo referente al grupo A, con una ostensible superioridad en cuanto a la eficacia del tratamiento en comparación con el grupo B (68,57 por ciento), en el que se utilizó la crema esteroidea al 2 por ciento

Sarna noruega: evolución y tratamiento / Norwegian scabies: evolution and treatment

Se realizó un estudio retrospectivo de 130 pacientes ingresados con el diagnóstico de escabiosis en 5 años, determinándose que 4 presentaban la variedad de sarna noruega; en el cuadro clínico de estos últimos predominó el eritema y la hiperqueratosis fisurada palmoplantar y el comprometimiento de áreas extensas de la piel. Mejoraron todos con la terapéutica antiescabiósica

Manifestaciones dermatológicas en pacientes con SIDA / Skin manifestation in AIDS patients

Se estudiaron 120 casos con test de Elisa positivo y manifestaciones clínicas de SIDA. De estos pacientes, 6 no tenían manifestaciones dermatológicas, 32 fueron niños y 88 adultos, destacándose como enfermedades dermatológicas más frecuentes entre los niños la candidiasis y las dermatitis, y en los adultos las enfermedades de trasmisión sexual. La pérdida de peso, las poliadenopatías, la anemia y las diarreas se presentaron en más del 50 porciento de los pacientes